.G protein-coupled receptors (GPCRs) are one of the most prevailing protein families in the human genome. These membrane proteins are essential in cell physiology, as they respond to an extraordinary diversity of extracellular signals, such as photons, odorants, protonated amines, peptides or glycoprotein hormones. As malfunction of GPCRs is commonly translated into pathological outcomes, these proteins constitute one of the most attractive pharmaceutical targets. However, our understanding of the ligand-induced molecular mechanisms of GPCR activation is hampered by the scarcity of structural data. In my research I aim to understand how extracellular ligands trigger the process of signal transduction in GPCRs. Through chemical interpretation of structural data, and by using a combination of structural bioinformatics, molecular dynamics and data-mining of structure and sequence databases, I extract as much information as possible from experimentally determined protein structures. This knowledge is used to design new experiments and to build experimentally testable models of GPCR function that will lead to a better understanding of ligand selectivity and efficacy.
Molecular signatures of G-protein-coupled receptors
Venkatakrishnan AJ, Deupi X, Lebon G, Tate CG, Schertler GF, Babu MM.
Stabilized G protein binding site in the structure of constitutively active metarhodopsin-II
Deupi X, Edwards P, Singhal A, Nickle B, Oprian D, Schertler G, Standfuss J.
Proceedings of the National Academy of Sciences USA 2012 Jan 3;109(1):119-24
Tracking G-protein-coupled receptor activation using genetically encoded infrared probes
Ye, S., Zaitseva, E., Caltabiano, G., Schertler, G. F. X., Sakmar, T. P., Deupi, X., and Vogel, R.
Nature 2010 464, 1386–1389